The objective of this study is to elucidate the basic mechanisms involved in the regulation of erythropoiesis and to apply this knowledge to human erythropoietic diseases. A marrow culture method has been used to study the action of the hormone on the cyclic AMP concentration of fetal liver cells. We have found no increase or decrease in the cellular cyclic AMP levels at 5 minutes and 30 minutes after the addition of erythropoietin to these cells. Epinephrine, however, did produce a 7 fold increase in the concentration of cyclic AMP. This shows that the assay method which we used was working properly and could detect an increase in cyclic AMP if it occurred after the addition of erythropoietin. These studies indicate that the hormone can produce a marked increase in hemoglobin production in vitro without any change in cellular cyclic AMP concentration. They also fail to support the hypothesis that cyclic AMP may be involved in the regulation of erythropoiesis by erythropoietin. We have also shown that Friend polycythemia virus produces a marked increase in splenic iron 59 uptake in fasted Balb/c mice. This increase is proportional to the amount of infectous plasma that is administered to the mice and provides a linear dose response curve. This effect can be used to assay infected plasma for the amount of virus present. The iron 59 assay, as compared to the spleen focus forming assay, is faster, less expensive, has a wider range and employs a more objective counting procedure. We have been able to use this procedure to monitor erythropoietic activity of Friend virus sedimented in a sucrose gradient and to partially purify the virus. We are now preceding to determine the mechanism of action of the virus by studying its effect on RNA and DNA synthesis in vivo. Since the Friend virus polycythemia in mice resembles polycythemia vera in human beings these studies may have application to the human disease.